The objective of this research is to elucidate the functions of the phosphorylation of lysine-rich (Hl) histone in determining the structure and activity of chromatin in the cell nucleus. Currently proposed projects are concentrated on the study of two types of Hl histone phosphorylation which are catalyzed by a cyclic AMP-independent, growth-associated kinase and by cyclic AMP-dependent protein kinase. The distribution of phosphate on growth-associated phosphorylation sites in Hl histone through the cell replication cycle will be determined using methodology which precludes the action of phosphatases during histone isolation. The effects of growth-associated Hl phosphorylation on chromatin structure will be studied by employing nuclease digestion with DNase II, and by examining the sedimentation properties of nucleosome oligomers. The localization of cyclic AMP-stimulated Hl histone phosphorylation in active and inactive regions of chromatin will be investigated, to assess the relationship of this type of Hl phosphorylation to increases in specific mRNA's. The mechanism for the activation and inactivation of growth-associated histone kinase activity which occurs in connection with the passage of cells through mitosis will be investigated in an in vitro system, and phosphatases which dephosphorylate growth-associated phosphorylation sites in Hl histone will be sought, in order to gain information on factors which regulate growth-associated Hl histone phosphorylation in cells.